Even with advances in screening and early detection, roughly 10 to 20 percent of men are diagnosed with high-grade disease, a Gleason score of 8 to 10. Two Hopkins urologists, Ashley Ross, M.D., Ph.D., and Ed Schaeffer, M.D., Ph.D., are looking for answers on the molecular level, hoping to find markers that will help identify aggressive disease early, and lay the groundwork for new ways to treat it.
“Even if it’s localized, prostate cancer has a wide range of aggressiveness,” says Ross. “The most powerful predictor of this is the Gleason sum,” or score, based on how the cells look to a pathologist under the microscope. “A low Gleason sum, even in the absence of intervention, is often associated with low risk of death, but a high Gleason sum can indicate a poor prognosis.”
Ross and Schaeffer began by using laser capture micro-dissection technology to isolate individual cells from the prostates of men who underwent prostatectomy at Johns Hopkins. “We compared the differences between cellular signatures of low- and high-Gleason disease,” says Schaeffer, “and then broadened the search to include prostatectomy specimens from other institutions to develop a master list of the genes and signaling pathways that characterize high-Gleason disease.”
The scientists are beginning to test candidate markers that could identify aggressive prostate cancer early, and to explore the use of novel therapies targeted against highgrade disease.